A trans-diagnostic perspective on obsessive-compulsive disorder

Abstract

Progress in understanding the underlying neurobiology of obsessive-compulsive disorder (OCD) has stalled in part because of the considerable problem of heterogeneity within this diagnostic category, and homogeneity across other putatively discrete, diagnostic categories. As psychiatry begins to recognize the shortcomings of a purely symptom-based psychiatric nosology, new data-driven approaches have begun to be utilized with the goal of solving these problems: specifically, identifying trans-diagnostic aspects of clinical phenomenology based on their association with neurobiological processes. In this review, we describe key methodological approaches to understanding OCD from this perspective and highlight the candidate traits that have already been identified as a result of these early endeavours. We discuss how important inferences can be made from pre-existing case-control studies as well as showcasing newer methods that rely on large general population datasets to refine and validate psychiatric phenotypes. As exemplars, we take 'compulsivity' and 'anxiety', putatively trans-diagnostic symptom dimensions that are linked to well-defined neurobiological mechanisms, goal-directed learning and error-related negativity, respectively. We argue that the identification of biologically valid, more homogeneous, dimensions such as these provides renewed optimism for identifying reliable genetic contributions to OCD and other disorders, improving animal models and critically, provides a path towards a future of more targeted psychiatric treatments.

Keywords: ERN; OCD; RDoC; goal-directed; trans-diagnostic.

Fig. 1.

Data from 706 obsessive-compulsive disorder (OCD) patients re-plotted with permission from Nestadt and colleagues (2009). Disorders assessed were obsessive-compulsive personality disorder (OCPD), generalized anxiety disorder (GAD), major depression (recurrent), tics, pathological skin picking, separation anxiety disorder, pathological nail biting, panic disorder, alcohol dependence, body dysmorphic disorder, substance dependence, trichotillomania, hypochondriasis, bipolar disorder. (a) Co-morbidity rates in a sample of OCD cases – 87.3% of patients met the criteria for another DSM diagnosis (note: this figure is probably higher as only select diagnoses were assessed). (b) The prevalence of specific co-morbid disorders within the OCD cohort.

Fig. 2.

Validating a trans-diagnostic dimension. (a) The strength of the association between self-report symptoms of various DSM disorders and deficits in goal-directed control. The pattern is strikingly non-specific. (b) The association between goal-directed deficits and three ‘trans-diagnostic symptom dimensions identified in a data-driven factor analysis. Factor 1 corresponds to ‘Anxious Depression’, Factor 2 is ‘Compulsive Behavior and Intrusive Thought’, and Factor 3 is ‘Social Withdrawal’. The association between Factor 2 (‘Compulsive Behavior and Intrusive Thought’) and deficits in goal-directed learning is greater than that of any of the nine DSM-inspired questionnaires and crucially, the relationship exhibits excellent specificity with respect to ‘non-compulsive’ aspects of psychopathology, i.e. Factor 1 (‘Anxious Depression’) and Factor 3 (‘Social Withdrawal’). Data reproduced with permission from Gillan et al. (2016b). *p < 0.05, **p < 0.01, ***p < 0.001.

Fig. 3.

A trans-diagnostic approach to obsessive-compulsive disorder (OCD). The predominant symptoms of OCD may result from complex interaction between independent trans-diagnostic dimensions, of which anxiety and compulsivity are good (but not the only) candidates. In this simplified schematic, we show just two putative trans-diagnostic psychiatric dimensions, there are of course many others. The task for basic research, outlined in the Research Domain Criteria initiative is to understand these dimensions at units of analysis, linking self-report symptoms (such as anxiety and compulsivity) to paradigms, physiology, circuits, cells, molecules and genes. GAD, Generalized anxiety disorder.